First of all, I’d like to mention that day before yesterday I wrote Prof. Gertz a quick note, telling him I’d written my first post about the meeting in Campi Bisenzio. He kindly wrote back, letting me know that my post was, and I quote, very accurate. Later that day, he sent me the newly published study about the Australian MGUS and SMM clinical trial results. How about that? I was blown away…still am. Thank youuuuu!
Ok, back to the meeting. Prof. Gertz also talked about heavy and light chain myeloma. The heavy chains (G and A) can be measured, as we know, in the blood; the light ones (kappa and lambda) in the 24-hour urine test that we know all too well…sigh.
While it’s not THE disease, the protein can be used as a good marker, as a sort of gauge for treatment, he said. As for kappa and lambda, they can occasionally spill into the kidney, damaging the kidney filter. 15% of myeloma patients have kidney damage, which can be measured via serum creatinine and the Blood Urea Nitrogen (BUN) test. As for heavy chains, G and A are too big to get into the kidney, so those patients don’t have kidney damage.
Then he spoke about BONE issues. As we know, there are two types of bone cells, osteoblasts, which build bone, and osteoclasts, which destroy it. As we get older, it’s normal to have an increase in osteoclast activity (I read that bone mineral loss begins after age 30…). What is NOT normal is what happens to myeloma folks. Myeloma produces chemicals that activate osteoclasts. Result: our bones lose minerals and become increasingly porous and brittle. He then spoke about the drugs that can help us when this occurs, such as Zometa, but since we all know about bisphosphonates, I didn’t take any notes.
Then he gave us the following scenario: let’s say our garden is full of weeds, but instead of using a 15 or even 30 ml mixture of a certain (toxic, clearly) weed killer, we spray a 250 ml mixture all over it. What will happen? Obviously, the entire garden will die. But hey, we can’t live without the garden. We need our white cells to fight infections, blablabla. So we have to be amazingly careful with quantities…(unless we’re facing a stem cell transplant, in which case things are different…you have to avoid melphalan until the stem cells are collected etc. etc. etc.).
At that point he went through the different classes of “weed killers”: 1. corticosteroids such as dexamethasone; 2. alkylating agents such as melphalan. These two classes started being used 50 years ago to treat myeloma patients. And for a long time, there was little else available. He highlighted the fact that Dex by itself, in high doses, is able to kill a whole bunch of myeloma cells. In fact, if my notes are correct, 50% of all the myeloma cells in 50% of all multiple myeloma patients. But that 50% of patients would pay a terribly high price for this MM cell “massacre,” including (and here the good professor had us chuckling, especially when he listed the first three options): never ever sleep again, fight with anyone in sight, eat all the time, develop a bunch of allergies and problematic side effects such as diabetes and high blood pressure…I forget what else, but the list went on and on. So that’s not really a good option, he said.
But nowadays we have a bunch of new drugs from which to choose. Let’s begin with 3. immunomodulatory drugs, such as thalidomide and its various descendants. He said that lenalidomide (Revlimid) is replacing thalidomide because of the irreversible peripheral neuropathy caused by the latter. But Rev has problems of its own: it can cause skin problems, diarrhea and leg cramps and can also have a negative effect on blood counts.
4. Proteasome inhibitors, such as Velcade and carfilzomib (the latter is being tested in investigational studies; 25, according to the clinical trial website). These block the “garbage disposal” = the proteasome in the myeloma cell, he said. What happens, therefore, is that the garbage starts building up inside the cell, which eventually gets “stuffed,” says “poof” and dies. (Okay, Prof. Gertz didn’t say some of this. “says “poof” and dies” is mine. 🙂 ) Great image. Incidentally, lest we forget!, curcumin is also a proteasome inhibitor… 🙂 Let’s see, what else? Prof. Gertz pointed out that the problem with Velcade is that it damages the nerves in the feet, whereas carfilzomib doesn’t. And of course, neither does curcumin (the references to curcumin are mine, of course, not the professor’s…).
5. He also spoke about a new, only oral proteasome inhibitor called MLN-9708. The goal, he said, is to have oral drugs, which are easier on, and more convenient for, the patient than intravenous drugs. I checked the clinical trials website, and MLN-9708 is currently being tested in six trials. Not a huge number, eh. Here’s an easy-to-read summary given by the Myeloma Beacon: http://goo.gl/64r6w
6. The second new drug he spoke about was Bendamustine, whose worst side effect, he said, are low blood counts (I actually read that there are a bunch of other unwelcome side effects, including nausea, fatigue, vomiting, diarrhea, fever, constipation, loss of appetite, cough, headache, unintentional weight loss, difficulty breathing, rashes, and stomatitis, as well as immunosuppression, anemia, and low platelet counts! Hmmm). Interesting history behind this drug. It was developed by East Germans and essentially ignored by the rest of the world for years…At any rate, I read this morning that it’s an alkylating agent…a nitrogen mustard (yeah, that’s right, mustard gas…sends shivers through me, I have to admit). Uhm…It’s being tested in 23 clinical trials right now…
And he also spoke of the importance of trying drug combinations, because of the issue of myeloma cell resistance. Again, we all know what that’s all about, so I didn’t bother taking any notes…
At that point the question and answer session began, and I took over from Vittorio. That means that I don’t have any more written notes. But I still have some good stuff…from what I remember, from the conversations we had at lunch (I was sitting right next to Prof. Gertz) and from my friend DB’s notes. I still haven’t mentioned what was said about curcumin, e.g. But that’ll have to wait until tomorrow…otherwise this post would be (again) too long. Besides, I have some work to do in the garden…while the sun is still up and about…Soooo…ciaooooooooo!
P.S. The above photo is of some flowers (these are daisies, and you can catch a glimpse of my pansies, too) I’ve begun planting in our rather bare-looking yard. Spring has arrived! 🙂